This invention relates to the use of diol lipid analogues, notably fatty acid esters of dihydric alcohols, as physiologically compatible fat replacements in foods and pharmaceuticals.
Although most lipids are derivatives of glycerol, many organisms of animal, plant and microbial origin also contain small amounts of lipids that are derivatives of diols. These include mono- and diacyl esters and mixed alkyl and alkenyl ester fatty acid derivatives of ethylene glycol, 1,2- and 1,3-propanediols, 1,3- 1,4- and 2,3-butanediols, and 1,5-pentanediol isolated from such widely differing tissues as mutton fat, fish liver, egg yolks, corn seeds, yeast and rat liver (Gurr, M. I., and James, A. T., Lipid Biochemistry, 3rd ed., Chapman and Hall, New York, 1980, pp. 91-92). These lipids, first separated from neutral lipid components using high-temperature gas-liquid chromatography, were named "diol lipids" (Bergelson, L. D., et al. 116 Biochim. Biophys. Acta 511 (1966)). Diol lipids have since been discovered among the ionic lipids (e.g., diol lipid analogues of phosphatidyl choline and phosphatidylethanolamine, diol choline plasma-logen, acylated diol galactosides, and diol lipoamino acids), and generally comprise a concentration of 0.5 to 1.5% that of glycerol derivatives (Smith, E. L., et al., Principles of Biochemistry: General Aspects, 7th ed., McGraw-Hill, New York, 1983, p. 117). Skin surface lipids can contain much higher concentrations (25-30% and above; see Nikkari, T., and Haahti, E., 164 Biochim. Biophys. Acta. 294 (1968) and Brind, J. L., et al. 84B Comp. Biochem. Physiol. 403 (1986)).
Diol lipids have not figured into reported research that has focused on ways of providing edible fat replacements, substances with the same functional and organoleptic properties as natural fat, but not the calories. (For recent reviews, see Hamm, D. J., 49 J. Food Sci. 419 (1984), Haumann, B. F., 63 J. Amer. Oil Chem. Soc. 278 (1986), and LaBarge, R. G., 42 Food Tech. 84 (1988).) A major strategy for developing low calorie replacement fats has been to structurally re-engineer the conventional triglycerides in such a way as to retain their conventional functional properties in foods, while removing their susceptibility toward hydrolysis or subsequent absorption during digestion. To this end, the ester linkages have been reversed (e.g., malonates in U.S. Pat. No. 4,482,927 to Fulcher and trialkoxytricarballylates in U.S. Pat. No. 4,508,746 to Hamm); the ester linkages have been replaced by ether linkages (U.S. Pat. No. 3,818,089 to Bayley and Carlson and Can. Pat. No. 1,106,681 to Trost); ethoxy and propoxy groups have been inserted between the fatty acids and the glycerol backbone (U.S. Pat. No. 4,861,613 to White and Pollard); the glycerol moiety has been replaced with alternate polyols (e.g., pentaerythritol in U.S. Pat. No. 2,962,419 to Minich, sugars in U.S. Pat. No. 3,600,186 to Mattson and Volpenhein and U.S. Pat. No. 4,840,815 to Meyer, et al., and polyglycerol in U.S. Pat. No. 3,637,774 to Babayan and Lehman); and the fatty acids have been replaced with alternate acids (e.g., branched acids as described in U.S. Pat. No. 3,579,548 to Whyte).
A second major approach to the development of a low calorie fat has been to explore or synthesize nonabsorbable polymeric materials structurally unlike triglycerides, but having physical properties similar to edible fat. Mineral oil was disclosed as early as 1894 (U.S. Pat. No. 519,980 to Winter), and, more recently, polydextrose (U.S. Pat. No. 4,631,196 to Zeller), polyglucose and polymaltose (U.S. Pat. No. 3,876,794 to Rennhard), polysiloxane (Eur. Pat. Ap. No. 205,273 to Frye), jojoba wax (W. Ger. Pat. No. 3,529,564 to Anika), polyoxyalkylene esters (U.S. Pat. No. 4,849,242 to Kershner), and polyvinyl alcohol esters (U.S. Pat. No. 4,915,974 to D'Amelia and Jacklin) have been suggested.
Nondigestible or nonabsorbable fat replacements have proved disappointing when tested in feeding trials, where gastrointestinal side effects occurred, in some cases so extreme that frank anal leakage was observed. Nondigestible fats appear to act as a laxative and are expelled from the body, eliciting foreign body reactions like those early documented for mineral oil (Stryker, W. A., Arch. Path. 31: 670-692 (1941), more recently summarized in Goodman and Gilman's Pharmacological Basis of Therapeutics, 7th ed., Macmillan Pub. Co., N.Y. 1985, pp. 1002-1003). In the U.S.D.A.'s assessment of the caloric availability and digestibility of a series of new-type fats in the 1960's (e.g., amylose fatty acid esters, diglyceride esters of succinic, fumaric, and adipic acids, and polymeric fats from stearic, oleic and short-chain dibasic acids; see Booth, A. N., and Gros, A. T., J. Amer. Oil Chem. Soc. 40: 551-553 (1963) and the references cited therein), rats fed the experimental fats exhibited undesirable gastrointestinal side effects similar to what had already been observed with mineral oil consumption by people. In several of the balance studies, the diarrhea was so extreme that digestibility coefficients could not be calculated (ibid., Table I, p. 552).
Polyglycerol and polyglycerol esters have been suggested, not only as fat replacements, but also as fecal softening agents (U.S. Pat. No. 3,495,010 to Fossel). A number of remedies have been recommended to combat the anal leakage observed when sucrose polyesters are ingested (e.g., employing cocoa butters, U.S. Pat. No. 4,005,195 to Jandacek, incorporating saturated fatty groups, Eur. Pat. Ap. No. 233,856 to Bernhardt, or mixing residues, U.S. Pat. No. 4,797,300 to Jandacek, et al.). Saturated fatty acids have been disclosed as anti-anal leakage agents for polyorganosiloxane fat substitutes (U.S. Pat. No. 4,925,692 to Ryan), and dietary fiber preparations have been incorporated into foodstuffs containing other fat replacements to help inhibit the diarrheal effect (U.S. Pat. No. 4,304,768 to Staub et al. and Eur. Pat. Ap. No. 375,031 to DeBoer and Kivits). Partially digestible fat replacements have also been suggested (U.S. Pat. No. 4,830,787 to Klemann and Finley; U.S. Pat. No. 4,849,242, cited above; and U.S. Pat. No. 4,927,659 to Klemann, et al.).